The new 3D tissue analysis of thyroid tumors is still unfamiliar to pathologists. Instead of cutting the removed tissue into thin slices and viewing them two-dimensionally under the microscope as before, they can now examine the entire tissue sample virtually on the screen and rotate it as required to identify pathological changes. This has been made possible by so-called non-invasive histopathological 3D imaging. “The special thing about this method is that it can analyze complete biopsy blocks of a tumor in three dimensions in a short time without changing or destroying the tissue. This means that the sample can still be used for further molecular biological examinations,” says Robert Zboray, group leader at Empa's Center for X-ray Analysis, who developed this technology.

Personalized treatment

Together with pathologists from the University of Bern, Zboray was able to demonstrate that his new method can detect clinically relevant tissue characteristics in thyroid tumors. X-ray phase-contrast micro-computed tomography (micro-CT) makes even the smallest differences in soft tissue visible. These three-dimensional images of tissue samples are then analyzed using machine learning. The Empa researcher hopes that this will enable pathologists to make more precise diagnoses and prognoses. The greatest challenge is to treat patients as individually as possible - in other words, to avoid overtreatment of low-risk tumors and at the same time to treat and monitor patients with a higher risk appropriately.
Around 300 million people worldwide are affected by thyroid cancer. However, tumor characteristics often differ from patient to patient. These measurable biochemical and molecular characteristics of a tumor are known as biomarkers. They help to detect cancer at an early stage or indicate how aggressively a tumor can grow and which therapy it may respond to.

Examining tissue from the past

A major advantage of 3D analysis is that it also detects tumor characteristics in the deeper tissue layers that may be overlooked by conventional methods. “When encapsulated thyroid tumors grow aggressively and quickly, they often break into the surrounding healthy tissue and even invade blood vessels. Such vascular invasions are therefore often an indication of the malignancy and severity of the tumor,” explains Zboray. An early and more precise diagnosis enables doctors to act more quickly and in a more targeted manner, thus improving the patient's prognosis.
In collaboration with the University and Inselspital Bern, Zboray and his team examined a thyroid tumor sample from a patient who had recently died. This patient had been hospitalized in 2011 for a tumor that was classified as benign but later recurred in a malignant form. “Conventional sectional analysis missed capsular hernias deep in the tissue, which we were able to identify retrospectively using our method,” says Zboray. Based on this finding, a retrospective study of such recurrence cases is now being carried out, in which samples from patients across Europe are being examined who, despite initially harmless findings, later developed serious tumors. Thanks to the generous support of the Mirto Foundation, the Bank Vontobel Donation Foundation, the Foundation for Research in Tumor Diagnostics and Prevention, the Dr. Hans Altschüler Foundation and four other foundations, the study can be carried out.

An ideal addition

According to Robert Zboray, the new 3D tissue analysis can be seamlessly integrated into the clinical workflow and ideally complements conventional sectional analysis. “Established procedures are firmly anchored in everyday medical practice. Our technology is not intended to disrupt these processes, but to offer additional benefits.” The development of new technologies for personalized medicine is also the goal of “Personalized Health and Related Technologies” (PHRT), a strategic research focus of the institutions of the ETH Domain, in which the project is embedded.
The technology also appears to be promising for other tumor types such as prostate cancer or lung cancer. Thanks to funding from the Swiss National Science Foundation (SNSF), Zboray can now test his three-dimensional histology technique in the metastasis of colorectal cancer. He would also like to replace complex molecular analyses with simpler imaging methods. “If we succeed in correlating the molecular “fingerprints” of the pathologically altered cell functions in the tumor tissues with imaging texture features in the micrometer range, we could link our technology directly to the underlying genetic changes in the future,” says Zboray, formulating his vision.